Certain physiological and cognitive traits occur much more frequently among the first degree relatives of schizophrenic patients than they do in the general population. These traits are not clinically harmful, but they are very useful scientifically, both as probes into the pathophysiology os schizophrenia, and as supplementary phenotypes in linkage analysis. The objective of this Program Project is to discover such traits, and to use them to increase our understanding of the pathophysiology and genetics of schizophrenia. Eye tracking disorder and impaired spatial working memory are example of traits that aggregate in the first degree relatives of schizophrenic patients. Since they are frequently found in relatives who do not express any schizophrenia-like pathology, they cannot be secondary effects of schizophrenia, but are related in a unknown way to the biological processes underlying the disease. In this Program Project, eye tracking disorder, spatial working memory, cognitive interference, dysmorphology, and event-related potentials are studied in the relatives of schizophrenic patients, after thorough clinical assessment, both in the psychophysiology laboratory and through fMRI imaging. Traits that run in the families of to schizophrenic patients have genetic importance as well. The search for genetic markers linked schizophrenia has been hindered by the low rate at which the illness recurs in the families of schizophrenic patients. These co-segregating traits are generally much more common among family members, making them useful as genetic indicators. The sample drawn from the McLean Hospital, where the Program Project is based, but investigators form other Harvard institutions also contribute to the measurements and analyses, including the Vision Sciences Laboratory in the Department of Psychology, the Statistics Department of the Faculty of Arts and Science, the Eunice Kennedy Shrive Center for Mental Retardation, and the Molecular Neurogenetics Unit at the Massachusetts General Hospital.